Nagashige M, Ushigome F, Koyabu N, Hirata K, Kawabuchi M, Hirakawa T, Satoh S, Tsukimori K, Nakano H, Uchiumi T, Kuwano M, Ohtani H, Sawada Y
Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582 Fukuoka, Japan.
Placenta. 2003 Nov;24(10):951-8. doi: 10.1016/s0143-4004(03)00170-x.
The placental trophoblast is considered to act as a barrier between mother and fetus, mediating the exchange of various materials across the placenta. ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp) and multidrug-resistance protein (MRP) are expressed in the placenta and function as efflux transport systems for xenobiotics. In the present study, we aimed to determine the localization of MRP1 in the human placenta in comparison with that of P-gp. Western blotting analysis with human placental membrane vesicles indicated that P-gp and MRP1 are localized on the brush-border membranes and basal membranes, respectively. Immunohistochemical analysis with human normal full-term placenta showed that anti-P-gp monoclonal antibody F4 stained the brush-border side of the trophoblast cells, whereas anti-MRP1 monoclonal antibody MRPr1 stained the basal side. These results confirm that P-gp and MRP1 are located on the brush-border membranes and basal membranes, respectively, of human full-term placental trophoblast. MRP1 was also detected on the abluminal side of blood vessels in the villi. Accordingly, MRP1 may play a role distinct from that of P-gp, which is considered to restrict the influx of xenobiotics into the fetus.
胎盘滋养层被认为是母体与胎儿之间的一道屏障，介导各种物质通过胎盘进行交换。诸如P-糖蛋白（P-gp）和多药耐药蛋白（MRP）等ATP结合盒（ABC）转运蛋白在胎盘中表达，并作为外源性物质的外排转运系统发挥作用。在本研究中，我们旨在确定MRP1在人胎盘中相对于P-gp的定位。用人胎盘膜囊泡进行的蛋白质印迹分析表明，P-gp和MRP1分别定位于刷状缘膜和基底膜上。用人正常足月胎盘进行的免疫组织化学分析表明，抗P-gp单克隆抗体F4对滋养层细胞的刷状缘侧进行染色，而抗MRP1单克隆抗体MRPr1对基底侧进行染色。这些结果证实，P-gp和MRP1分别位于人足月胎盘滋养层的刷状缘膜和基底膜上。在绒毛血管的无腔侧也检测到了MRP1。因此，MRP1可能发挥与P-gp不同的作用，P-gp被认为可限制外源性物质流入胎儿体内。
